Notch controls the cell cycle to define leader versus follower identities during collective cell migration
- King's College London, United Kingdom
- The Francis Crick Institute, United Kingdom
- University of Bath, United Kingdom
- The University of Chicago, United States
- University of Padova, Italy
- University of Chicago, United States
Abstract
Coordination of cell proliferation and migration is fundamental for life, and its dysregulation has catastrophic consequences, such as cancer. How cell cycle progression affects migration, and vice-versa, remains largely unknown. We address these questions by combining in-silico modelling and in vivo experimentation in the zebrafish Trunk Neural Crest (TNC). TNC migrate collectively, forming chains with a leader cell directing the movement of trailing followers. We show that the acquisition of migratory identity is autonomously controlled by Notch signalling in TNC. High Notch activity defines leaders, while low Notch determines followers. Moreover, cell cycle progression is required for TNC migration and is regulated by Notch. Cells with low Notch activity stay longer in G1 and become followers, while leaders with high Notch activity quickly undergo G1/S transition and remain in S-phase longer. In conclusion, TNC migratory identities are defined through the interaction of Notch signalling and cell cycle progression.
Data availability
The model code is accessible at https://github.com/Bentley-Cellular-Adaptive-Behaviour-Lab/NeuralCrestCpp. The code used to perform the LDA analysis is accessible in the supplementary files. All numerical data used in the figures is accessible in the supplementary data source file.
Article and author information
Author details
Christopher Revell
Francesco Argenton
Funding
Medical Research Council (G1000080/1)
- Zain Alhashem
Royal Society (2010/R1)
- Zain Alhashem
Wellcome Trust (207630/Z/17/Z)
- Zain Alhashem
Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institues of Health (T32HD055164)
- Manuel Rocha
Eucine Kennedy Shiver National Institute of Child Health & Human Development of the National Institues of Health (F31HD097957)
- Manuel Rocha
Cancer Research UK (FC001751)
- Dylan Feldner-Busztin
Medical Research Council (FC001751)
- Dylan Feldner-Busztin
Wellcome Trust (FC001751)
- Dylan Feldner-Busztin
Biotechnology and Biological Sciences Research Council (BB/S015906/1)
- Robert Kelsh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Zebrafish were maintained in accordance with UK Home Office regulations UK Animals (Scientific Procedures) Act 1986, amended in 2013 under project license P70880F4C.
Copyright
© 2022, Alhashem et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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